scholarly journals Opioid Induced Hyperalgesia Altered with Propofol Infusion

2014 ◽  
Vol 2;17 (2;3) ◽  
pp. E225-E228 ◽  
Author(s):  
Alan D. Kaye
Keyword(s):  
Animal Studies ◽  
Endocannabinoid System ◽  
Induction Agent ◽  
Aspartate Receptor ◽  
Randomized Controlled Studies ◽  
Potential Therapeutic Role ◽  
Opioid Induced Hyperalgesia ◽  
Key Words Analgesia ◽  
Excitatory Neurotransmission ◽  
High Doses

Propofol is a common induction agent that is utilized worldwide in the field of anesthesiology. In recent years, its potential therapeutic role in a variety of patient states has been demonstrated. Controversy exists regarding Propofol mediated analgesic and antihyperalgesic properties. Recent studies have suggested a variety of different mechanisms of action, including modulation of N-Methyl-D- Aspartate receptors and the endocannabinoid system. The N-Methyl-D- Aspartate receptor is part of a larger family of glutamate receptors and is an important mediator of excitatory neurotransmission. In the case presented, the pain experienced by the patient was not well-controlled, in spite of increasing doses of opioids, potentially due to superimposed opioid induced hyperalgesia. In the present case, we demonstrate a cycle of opioid induced hyperalgesia which was successfully affected with a Propofol infusion. Controversial reports exist in animal studies on the analgesic properties of Propofol. Randomized controlled studies in animal models studying the effect of Propofol on pain sensation have shown that Propofol possesses an analgesic effect. This clinical case demonstrates that Propofol could possibly have antihyperalgesic effects on opioid induced hyperalgesia caused by high-doses of chronic opioids and worsened by fentanyl. We postulate that a probable mechanism of complete pain relief after the procedure could be the inhibition of activity of the N-Methyl-DAspartate receptor by Propofol because it was the only agent the patient received during the procedure, causing a break of the cycle of opioid induced hyperalgesia. Additional research is required to clarify Propofol mediated or modulated analgesic properties in humans. Key words: Analgesia, hyperalgesia, opioids, propofol, antihyperalgesia, anesthesia

scholarly journals Effects of Simultaneous Reinforcement of Endocannabinoid and Cholinergic Systems on Anxiety-Like Behavior in Mice

2021 ◽  
Author(s):  
Siamak Shahidi ◽  
Asghar Dindar ◽  
Alireza Komaki ◽  
Reihaneh Sadeghian
Keyword(s):  
Elevated Plus Maze ◽  
Enzyme Inhibitor ◽  
Endocannabinoid System ◽  
Anxiolytic Effect ◽  
Control Group ◽  
Concurrent Administration ◽  
Elevated Plus Maze Test ◽  
Cholinergic Systems ◽  
Plus Maze ◽  
High Doses

Abstract ObjectiveAnxiety behavior is regulated by different neurotransmitter systems. There has been no direct relationship between endocannabinoid and cholinergic systems on anxiety in previous studies. This study investigated the effects of each of these systems separately and simultaneously using Donepezil (Cholinesterase inhibitor) and URB-597 (endocannabinoid degrading enzyme inhibitor) on anxiety-like behavior. MethodEighty-eight male mice were divided into eleven groups (n=8) including control (saline), diazepam (0.3 mg /kg), URB-597 (0.1, 0.3, or 1 mg /kg), donepezil (0.5, 1 or 2 mg/kg) and the combination of the two drugs at low, medium and high doses. All treatments were injected intraperitoneally 30 minutes before the elevated plus maze test. ResultsSeparate administration of URB597, donepezil or diazepam increased the number and time spent of open arms compared to the control group. Concurrent administration of URB and donepezil at low, medium and high doses did not change the number of open arms entries compared to the control group, but they reduced the number of entries to the closed arms. ConclusionsThese results suggest that strengthening any cholinergic or endocannabinoid system has anxiolytic effect similar to diazepam. However, the interaction of these two systems has fewer anxiolytic effects compared to the effects of each alone. It seems that these drugs alone may represent a strategy for the treatment of anxiety disorders.

Perioperative dilemma: Challenges of the management of a patient on mega doses of morphine and methadone

2014 ◽  
Vol 10 (1) ◽  
pp. 69 ◽  
Author(s):  
Alan David Kaye, MD, PhD, DABA, DABPM, DABIPP ◽  
Aymen A. Alian, MD ◽  
Nalini Vadivelu, MD ◽  
Keun Sam Chung, MD
Keyword(s):  
Back Pain ◽  
Case Report ◽  
High Dose ◽  
Successful Management ◽  
Present Case Report ◽  
Opioid Induced Hyperalgesia ◽  
History Of ◽  
High Doses

High doses of opioids are often needed in the management of cancer-related pain. A discussion of a patient’s perioperative opioid management and mechanisms contributing to opioid-induced hyperalgesia (OIH) are presented. In the present case report, a patient on high doses of opioids, including morphine and methadone, with severe worsening back pain and a history of increasing opioid requirements for the last 2 months due to metastatic leiomyosarcoma to the femur, spine, and neck is described. Use of high dose opioids is associated with numerous challenges, including tolerance. The successful management of this patient was multimodal and included the use of potent analgesics, N-methyl-D-aspartatereceptor antagonists, and the α-2 agonist clonidine.

scholarly journals THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amelia Dahlén ◽  
Mahdi Zarei ◽  
Adam Melgoza ◽  
Mahendra Wagle ◽  
Su Guo
Keyword(s):  
Nmda Receptor ◽  
Cannabinoid Receptor ◽  
Repetitive Behavior ◽  
Endocannabinoid System ◽  
Adult Zebrafish ◽  
Acute Effects ◽  
Cannabinoid Receptor 1 ◽  
Cannabinoid Receptor 2 ◽  
High Doses ◽  
Underlying Mechanisms

AbstractHigh doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC’s effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ‐aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model’s potential for elucidating the mechanistic relationship between Cannabis and psychosis.

scholarly journals The expression of cannabinoid-related genes in multiple disease cell lines

2019 ◽  
Author(s):  
Philip A. Arlen ◽  
Xingzhu Wu
Keyword(s):  
Cell Lines ◽  
Cognitive Processes ◽  
Expression Profiles ◽  
Endocannabinoid System ◽  
Gene Products ◽  
Pain Sensation ◽  
Potential Therapeutic Role ◽  
Cancerous Cells ◽  
The Brain ◽  
Disease Cell

AbstractThe endocannabinoid system comprises a series of ligands and receptors that have putative roles in regulating physiological and cognitive processes such as pre- and post-natal development, appetite, pain sensation, mood, and memory. Besides the endocannabinoids, these endogenous receptors are also capable of mediating the pharmacological effects of phytocannabinoids, which are derived from the cannabis plant. We sought to interrogate a panel of cell lines, representative of multiple human diseases, to characterize their cannabinoid-mediating gene expression. We found all lines expressed one or more gene product that rendered the cell potentially responsive to cannabinoids. Moreover, the expression profiles differed between normal and cancerous cells, as well as between cells derived from the brain, pancreas, and skin. Taken together, given the presence of one or more of these mediating gene products, our findings suggest a potential therapeutic role for phytocannabinoids.

scholarly journals α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

2019 ◽  
Vol 130 (5) ◽  
pp. 804-819 ◽  
Author(s):  
Meichun Deng ◽  
Shao-Rui Chen ◽  
Hong Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Spinal Dorsal Horn ◽  
Receptor Activity ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Analgesic Tolerance ◽  
Spinal Dorsal ◽  
Aspartate Receptor ◽  
C Terminus ◽  
Opioid Induced Hyperalgesia

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Chronic use of μ-opioid receptor agonists paradoxically causes both hyperalgesia and the loss of analgesic efficacy. Opioid treatment increases presynaptic N-methyl-d-aspartate receptor activity to potentiate nociceptive input to spinal dorsal horn neurons. However, the mechanism responsible for this opioid-induced activation of presynaptic N-methyl-d-aspartate receptors remains unclear. α2δ-1, formerly known as a calcium channel subunit, interacts with N-methyl-d-aspartate receptors and is primarily expressed at presynaptic terminals. This study tested the hypothesis that α2δ-1–bound N-methyl-d-aspartate receptors contribute to presynaptic N-methyl-d-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance. Methods Rats (5 mg/kg) and wild-type and α2δ-1–knockout mice (10 mg/kg) were treated intraperitoneally with morphine twice/day for 8 consecutive days, and nociceptive thresholds were examined. Presynaptic N-methyl-d-aspartate receptor activity was recorded in spinal cord slices. Coimmunoprecipitation was performed to examine protein–protein interactions. Results Chronic morphine treatment in rats increased α2δ-1 protein amounts in the dorsal root ganglion and spinal cord. Chronic morphine exposure also increased the physical interaction between α2δ-1 and N-methyl-d-aspartate receptors by 1.5 ± 0.3 fold (means ± SD, P = 0.009, n = 6) and the prevalence of α2δ-1–bound N-methyl-d-aspartate receptors at spinal cord synapses. Inhibiting α2δ-1 with gabapentin or genetic knockout of α2δ-1 abolished the increase in presynaptic N-methyl-d-aspartate receptor activity in the spinal dorsal horn induced by morphine treatment. Furthermore, uncoupling the α2δ-1–N-methyl-d-aspartate receptor interaction with an α2δ-1 C terminus–interfering peptide fully reversed morphine-induced tonic activation of N-methyl-d-aspartate receptors at the central terminal of primary afferents. Finally, intraperitoneal injection of gabapentin or intrathecal injection of an α2δ-1 C terminus–interfering peptide or α2δ-1 genetic knockout abolished the mechanical and thermal hyperalgesia induced by chronic morphine exposure and largely preserved morphine’s analgesic effect during 8 days of morphine treatment. Conclusions α2δ-1–Bound N-methyl-d-aspartate receptors contribute to opioid-induced hyperalgesia and tolerance by augmenting presynaptic N-methyl-d-aspartate receptor expression and activity at the spinal cord level.

Cannabinoids and Emotional Regulation

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Emotional Regulation ◽  
Stress Hormones ◽  
Endocannabinoid System ◽  
Small Scale ◽  
Post Traumatic Stress ◽  
Excitatory Neurotransmitter ◽  
Inhibitory Neurotransmitter ◽  
High Doses ◽  
Preclinical Animal Models ◽  
Regulation Of Emotion

Marijuana is often used for relaxation, therefore, it is not surprising that the endocannabinoid system is critically involved in the regulation of emotion, anxiety and mood. In preclinical animal models, THC and other CB1 agonists produce a biphasic effect on anxiety, with low doses reducing anxiety (by blocking the release of the excitatory neurotransmitter glutamate) and high doses promoting anxiety (by blocking the release of the inhibitory neurotransmitter, GABA). As well, CBD reduces anxiety in both preclinical and clinical research, but by a non-CB1 mechanism of action. One of the most promising treatments for cannabinoids is post-traumatic stress disorder (PTSD). Considerable preclinical animal research and small-scale clinical trials have shown that activation of the endocannabinod system may promote extinction of aversive memories. The endocannabinoid system regulates the action of the Hypothalamic-Pituitary-Adrenal (HPA) Axis, which controls the release of stress hormones.

Effect of Human Recombinant VWF Administration on Plasma ADAMTS13 Activities in Non-Human Primates and Rabbits

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4105-4105
Author(s):  
Katalin Varadi ◽  
Hanspeter Rottensteiner ◽  
Eva M Muchitsch ◽  
Alfred Weber ◽  
Herbert Gritsch ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Animal Studies ◽  
Von Willebrand Disease ◽  
Dependent Manner ◽  
Adamts13 Activity ◽  
High Doses ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Dose Dependent

Abstract Von Willebrand factor (VWF) is composed of a series of multimers, the sizes of which are regulated by the plasma metalloprotease ADAMTS13. Reports suggest that a transient increase in VWF levels, triggered for instance by DDAVP treatment, will result in a decrease in ADAMTS13 activity. This phenomenon is widely believed to be due to ADAMTS13 being exhausted when confronted with an excess of substrate. Treating patients who have type 3 von Willebrand disease with a recombinant human von Willebrand factor (rVWF) that has not yet been exposed to ADAMTS13 might thus cause a drop in ADAMTS13 levels. We therefore tested whether a rise in VWF concentrations to supraphysiological levels caused by administration of rVWF could influence endogenous ADAMTS13 levels in animal models. Various doses of human rVWF (300, 600, and 1200 RCo IU/kg BW) were injected into rabbits and cynomolgus monkeys and plasma samples were collected at a range of time points. As expected, VWF antigen rose sharply in a dose-dependent manner (~25 IU/ml VWF:Ag for the highest dose, 15 min after injection) and then declined gradually (~7 IU/ml VWF:Ag for the highest dose, 18 hours after injection). When these samples were tested for ADAMTS13 activity using the FRETS assay, no relevant changes were observed throughout the entire test period in the rabbit or in the monkey samples, indicating that rVWF, even at high doses, did not compromise ADAMTS13 activity. Both rabbit and cynomolgus ADAMTS13 recognized human rVWF as the specific cleavage products were detectable by electrophoresis at all doses administered. These animal studies thus indicate that an excess of intravenously administered rVWF leading to supraphysiological levels does not exhaust ADAMTS13.

scholarly journals The role of cannabinoids and endocannabinoid system in the treatment of epilepsy

2015 ◽  
Vol 23 (2) ◽  
pp. 131-138
Author(s):  
Monika Pędracka ◽  
Jacek Gawłowicz
Keyword(s):  
Side Effects ◽  
Animal Studies ◽  
Endocannabinoid System ◽  
Seizure Threshold ◽  
Gamma Aminobutyric Acid ◽  
Double Blind ◽  
Model Studies ◽  
Treatment Of Epilepsy ◽  
New Antiepileptic Drugs

Summary Introduction. The treatment of epilepsy is still a major challenge. Despite the introduction of many new antiepileptic drugs, approximately 30% of patients still remain drug resistant. In the absence of a satisfactory therapy outcome, which is sometimes associated with numerous side effects, there is a need for new and effective drugs with low toxicity. Cannabinoids have been shown in preliminary animal model studies and in studies of patients with epilepsy to have antiepileptic activity. Aim. The aim of this paper is to review current reports on the role of the endocannabinoid system and cannabinoids in the treatment of epilepsy. Methods. Articles from PubMed and Scopus published up to 2015 concerning the role of cannabinoids and the endocannabinoid system in the treatment of epilepsy are reviewed. Review and Discussion. Cannabis has been used for thousands of years in the treatment of various diseases. They contain cannabinoids, which act on the endocannabinoid system which regulates many biochemical and physiological processes. By affecting glutamate and gamma-aminobutyric acid (GABA) neurotransmission cannabinoids have the ability to affect seizure threshold. The best known cannabinoid is cannabidiol, which inhibits the occurrence of seizures without causing significant side effects in humans and animals. However, only a small number of double blind, randomized and placebo controlled studies have been published to date. Conclusions. The role of cannabinoids in the treatment of epilepsy is not well defined because these substances have shown pro-convulsive actions in some animal studies and also there are not many randomized trials performed to date. The existing human data do not support the conclusion that cannabinoids are effective and safe in the treatment of epilepsy, but do encourage further studies on a larger group of patients.

Too Much of a Good Thing? Treating the Emerging Syndrome of Opioid-Induced Hyperalgesia

2008 ◽  
Vol 21 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Robert Leonard ◽  
Helen Kourlas
Keyword(s):  
Chronic Pain ◽  
Management Strategies ◽  
Treatment Strategies ◽  
Opioid Therapy ◽  
Medical Subject Headings ◽  
Opioid Rotation ◽  
Seek Health Care ◽  
Aspartate Receptor ◽  
Opioid Induced Hyperalgesia ◽  
Very High

Pain is the primary reason individuals seek health care, and chronic pain is the leading cause of disability. Patients with chronic pain often require treatment with strong analgesics, including opioids. Mounting evidence shows that very high opioid doses or rapidly escalating doses may lead to a paradoxical syndrome of increasing pain that is nonresponsive to opioid therapy. A review of the published literature describing the phenomenon of opioid-induced hyperalgesia was conducted, and management strategies were reviewed. A systematic search of PubMed using Medical Subject Headings terms to narrow search criteria identified 3 treatment strategies. The strategies evaluated in this literature review include opioid rotation, coadministration of N-methyl-D-aspartate receptor antagonists, and coadministration of opioid antagonists. Further research is needed to draw conclusive recommendations. As of now, the safest and most effective treatment strategy showing the best evidence involves the use of opioid rotation.

scholarly journals Cannabis and Inflammation in HIV: A Review of Human and Animal Studies

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1521
Author(s):  
Ronald J. Ellis ◽  
Natalie Wilson ◽  
Scott Peterson
Keyword(s):  
Myocardial Infarction ◽  
Adverse Effects ◽  
Animal Studies ◽  
Endocannabinoid System ◽  
Cannabis Use ◽  
Review Of The Literature ◽  
Barrier Integrity ◽  
Persistent Inflammation ◽  
Anti Inflammatory ◽  
The Impact

Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut–blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.

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